Tumor-specific cytotoxic T lymphocytes (CTLs) can prevent or eradicate tumors in a number of experimental systems and in patients with cancer (1-3). Clinical trials have demonstrated that 35% of patients with melanoma treated with specific, tumor-reactive lymphocytes can achieve either partial or complete tumor regression (4). The antigens recognized by the T cells have, in some cases, been identified (5, 6). Although cancer cells may express tumor-associated antigens (TAAs), CTLs directed against TAAs are not efficiently elicited by the growing tumor and, therefore, the immune system fails to control tumor growth. Thus, it appears that tumor cells lack either immunogenicity and/or the appropriate co-stimulation required for CTL activation.
In contrast to tumor cells, viruses are strong inducers of cellular immune responses. Thus, activation of the tumor-directed CTL response by vaccination with recombinant viruses expressing tumor-associated antigens is a promising approach for the prevention and treatment of malignancies. Viral vaccine vectors that have been successfully used in experimental cancer models include poxviruses, adenoviruses, picornaviruses and influenza viruses (7-10). However, because each vaccine vector may present its own set of beneficial and adverse properties, the search for new vectors continues to be an active area of research. For example, clinical use of some vectors currently under study may be limited by their record of safety, efficacy, potential oncogenicity or induction of immunosuppression. In addition, pre-existing immunity against the vector could hinder the potency of treatment (8, 11), and therefore alternative viral vectors are needed.
There is a need in the field for viral vectors that can be used to induce immunity to a wide variety of antigens, including those present on tumors. The present invention addresses this need, and provides related advantages as well.